Antibacterial antiplaque, anticalculus oral composition

ABSTRACT

An oral composition such as a dentifrice, mouthwash, lozenge or chewing gum containing a polyphosphate anticalculus agent, such as tetraalkali metal pyrophosphate and antibacterial antiplaque agent compatible therewith. The antiplaque agent is a substantially water-insoluble noncatationic antibacterial agent such as 2,4,4&#39;-trichloro-2 1  -hydroxydiphenyl ether (Triclosan).

This application is a continuation of application Ser. No. 07/346,258,filed May 1, 1989, now U.S. Pat. No. 5,043,154, which is a continuationof application Ser. No. 07/008,901, filed Jan. 30, 1987, and nowabandoned.

This invention relates to an antibacterial antiplaque anticalculus oralcomposition. More particularly, it relates to an oral compositioncontaining a polyphosphate anticalculus (that is, antitartar) agent anda compatible antibacterial agent effective to inhibit plaque.

In U.S. Pat. Nos. 4,627,977 to Gaffar et al; 4,515,772 to Parran et al;and 4,323,551 to Parran, oral compositions are described which includevarious polyphosphate compounds. In the patent to Gaffar et al, a linearmolecularly dehydrated polyphosphate salt is employed in conjunctionwith a fluoride ion-providing source and a synthetic linear polymericpolycarboxylate to inhibit calculus formation.

In the patents to Parran et al and to Parran water soluble dialkalimetal pyrophosphate alone or mixed with tetraalkali metal pyrophosphateis employed.

Oral compositions which inhibit calculus formation on dental surfacesare highly desirable since calculus is one of the causitive factors inperiodontal conditions. Thus, its reduction promotes oral hygiene.

Dental plaque is a precursor of calculus. Unlike calculus, however,plaque may form on any part of the tooth surface, particularly includingat the gingival margin. Hence, besides being unsightly, it is implicatedin the occurence of gingivitis.

Accordingly, it would be highly desirable to include antimicrobialagents which have been known to reduce plaque in oral compositionscontaining anticalculus agents. Indeed, this has been described in U.S.Pat. No. 4,022,880 to Vinson et al, wherein a compound providing zincions as an anticalculus agent is admixed with an antibacterial agenteffective to retard the growth of plaque bacteria. A wide variety ofantibacterial agents are described with the zinc compounds includingcationic materials such as guanides and quaternary ammonium compounds aswell as non-cationic compounds such as halogenated salicylanilides andhalogenated hydroxydiphenyl ethers.

Hitherto, the cationic antibacterial materials such as chlorhexidine,benzethonium chloride and cetyl pyridinium chloride have been thesubject of greatest investigation as antibacterial antiplaque agents.However, in spite of their being used in conjunction with zincanticalculus agent, they are not effective when used with anionicmaterials such as polyphosphate anticalculus agent. This ineffectivenessis considered to be quite surprising as polyphosphates are chelatingagents and the chelating effect has previously been known to increasethe efficacy of cationic antibacterial agents. (see e.g. Disinfection,Sterilization and Preservation, 2nd Ed., Black, 1977, page 915 andInhibition and Destruction of the Microbial Cell, Hugo, 1971, page 215).Indeed, quaternary ammonium compound is present in the plaque controlmouthwash containing pyrophosphate of U.S. Pat. No. 4,323,551 andbis-biguanide antiplaque agent is suggested in the anticalculuspyrophosphate oral composition of U.S. Pat. No. 4,515,772.

In view of the surprising incompatibility of cationic antibacterialagents with polyphosphates present as anticalculus agents, it was quiteunexpected that other antibacterial agent would be effective.

It is an advantage of this invention that certain antibacterial agentsare effective in anticalculus oral compositions to inhibit plaqueformation.

It is a further advantage of this invention that a composition isprovided which is effective to reduce plaque and calculus formation.

It is a further advantage of this invention that an antiplaque,anticalculus oral composition is provided which is effective to reducethe occurrence of gingivitis.

Additional advantages of this invention will be apparent fromconsideration of the following specification.

In accordance with certain of its aspects this invention relates to anoral composition comprising in an orally acceptable vehicle, aneffective anticalculus amount of material comprising at least one linearmolecularly dehydrated polyphosphate salt as essential anticalculusagent and an effective antiplaque amount of a substantially waterinsoluble noncationic antibacterial agent selected from the groupconsisting of halogenated diphenyl ethers, phenolic compounds, benzoateesters, and halogenated carbanilides.

Typical examples of antibacterial agents which are particularlydesirable from considerations of antiplaque effectiveness, safety andformulation are:

Halogenated Diphenyl Ethers

2',4,4'-trichloro-2-hydroxy-diphenyl ether (Triclosan)

2,2'-dihydroxy-5,5'-dibromo-diphenyl ether.

Phenolic Compounds

including phenol and its homologs, mono-and poly-alkyl and aromatichalophenols, resorcinol and its derivatives, bisphenolic compounds andhalogenated salicylanilides

Phenol and its Homologs

Phenol

2 Methyl-Phenol

3 Methyl-Phenol

4 Methyl-Phenol

4 Ethyl-Phenol

2,4-Dimethyl-Phenol

2,5-Dimethyl-Phenol

3,4-Dimethyl-Phenol

2,6-Dimethyl-Phenol

4-n-Propyl-Phenol

4-n-Butyl-Phenol

4-n-Amyl-Phenol

4-tert-Amyl-Phenol

4-n-Hexyl-Phenol

4-n-Heptyl-Phenol

Mono- and Poly-Alkyl and Aromatic Halophenols

Methyl-p-Chlorophenol

Ethyl-p-Chlorophenol

n-Propyl-p-Chlorophenol

n-Butyl-p-Chlorophenol

n-Amyl-p-Chlorophenol

sec-Amyl-p-Chlorophenol

n-Hexyl-p-Chlorophenol

Cyclohexyl-p-Chlorophenol

n-Heptyl-p-Chlorophenol

n-Octyl-p-Chlorophenol

o-Chlorophenol

Methyl-o-Chlorophenol

Ethyl-o-Chlorophenol

n-Propyl-o-Chlorophenol

n-Butyl-o-Chlorophenol

n-Amyl-o-Chlorophenol

tert-Amyl-o-Chlorophenol

n-Hexyl-o-Chlorophenol

n-Heptyl-o-Chlorophenol

p-Chlorophenol

o-Benzyl-p-Chlorophenol

o-Benzyl-m-methyl-p-Chlorophenol

o-Benzyl-m, m-dimethyl-p-Chlorophenol

o-Phenylethyl-p-Chlorophenol

o-Phenylethyl-m-methyl-p-Chlorophenol

3-Methyl-p-Chlorophenol

3,5-Dimethyl-p-Chlorophenol

6-Ethyl-3-methyl-p-Chlorophenol

6-n-Propyl-3-methyl-p-Chlorophenol

6-iso-Propyl-3-methyl-p-Chlorophenol

2-Ethyl-3,5-dimethyl-p-Chlorophenol

6-sec Butyl-3-methyl-p-Chlorophenol

2-iso-Propyl-3,5-dimethyl-p-Chlorophenol

6-Diethylmethyl-3-methyl-p-Chlorophenol

6-iso-Propyl-2-ethyl-3-methyl-p-Chlorophenol

2-sec Amyl-3,5-dimethyl-p-Chlorophenol

2-Diethylmethyl-3.5-dimethyl-p-Chlorophenol

6-sec Octyl-3-methyl-p-Chlorophenol

p-Bromophenol

Methyl-p-Bromophenol

Ethyl-p-Bromophenol

n-Propyl-p-Bromophenol

n-Butyl-p-Bromophenol

n-Amyl-p-Bromophenol

sec-Amyl-p-Bromophenol

n-Hexyl-p-Bromophenol

cyclohexyl-p-Bromophenol

o-Bromophenol

tert-Amyl-o-Bromophenol

n-Hexyl-o-Bromophenol

n-Propyl-m,m-Dimethyl-o-Bromophenol

2-Phenyl Phenol

4-chloro-2-methyl phenol

4-chloro-3-methyl phenol

4-chloro-3,5-dimethyl phenol

2,4-dichloro-3,5-dimethylphenol

3,4,5,6-terabromo-2-methylphenol

5-methyl-2-pentylphenol

4-isopropyl-3-methylphenol

5-chloro-2-hydroxydiphenylmethane

Resorcinol and its Derivatives

Resorcinol

Methyl-Resorcinol

Ethyl-Resorcinol

n-Propyl-Resorcinol

n-Butyl-Resorcinol

n-Amyl-Resorcinol

n-Hexyl-Resorcinol

n-Heptyl-Resorcinol

n-Octyl-Resorcinol

n-Nonyl-Resorcinol

Phenyl-Resorcinol

Benzyl-Resorcinol

Phenylethyl-Resorcinol

Phenylpropyl-Resorcinol

p-Chlorobenzyl-Resorcinol

5-Chloro-2,4-Dihydroxydiphenyl Methane

4'-Chloro-2,4-Dihydroxydiphenyl Methane

5-Bromo-2,4-Dihydroxydiphenyl Methane

4'-Bromo-2,4-Dihydroxydiphenyl Methane

Bisphenolic Compounds

2,2'-methylene bis (4-chlorophenol)

2,2'-methylene bis (3,4,6-trichlorophenol)

2,2'-methylene bis (4-chloro-6-bromophenol)

bis (2-hydroxy-3,5-dichlorophenyl) sulfide

bis (2-hydroxy-5-chlorobenzyl) sulfide

Halogenated Carbanilides

3,4,4'-trichlorocarbanilide

3-trifluoromethyl-4,4'-dichlorocarbanilide

3,3',4-trichlorocarbanilide

The antibacterial agent is present in the oral composition in aneffective antiplaque amount, typically about 0.01-5% by weight,preferably about 0.03-1%. The antibacterial agent is substantiallywater-insoluble, meaning that its solubility is less than about 1% byweight in water at 25° C. and may be even less than about 0.1%. Ifanionizable group is present solubility is determined at a pH at whichionization does not occur.

The preferred halogenated diphenyl ether is Triclosan. The preferredphenolic compound are hexyl resorcinol, 2,2'-methylenebis(4-chloro-6-bromophenol). The most preferred antibacterial antiplaquecompound is Triclosan. Triclosan is disclosed in aforementioned U.S.Pat. No. 4,022,880 as an antibacterial agent in combination with ananticalculus agent which provides zinc ions. It is also disclosed as anantiplaque agent in a dentifrice formulated to contain a lamellar liquidcrystal surfactant phase having a lamellar spacing of less than 6.0 mmand which may optionally contain a zinc salt in published EuropeanPatent application 0161898 of Lane et al and in a dentifrice containingzinc citrate trihydrate in published European Patent Application 0161899to Saxton.

The linear molecularly dehydrated polyphosphate salts operative hereinas anticalculus agents are well known, being generally employed in theform of their wholly or partially neutralized water soluble alkali metal(e.g. potassium and preferable sodium) or ammonium salts, and anymixtures thereof. Representative examples include sodiumhexametaphosphate, sodium tripolyphosphate, disodium diacid, trisodiummonoacid and tetrasodium pyrophosphates and the like. They are generallyemployed in the instant oral compositions in approximate weight amountsof 0.1 to 7%, preferably 2 to 7%.

Particularly desirable anticalculus agents are tetraalkali metalpyrophosphates, including mixtures thereof, such as tetrasodiumpyrophosphate, tetrapotassium pyrophosphate and mixtures thereof. Ananticalculus agent comprising about 4.3% to about 7% by weight of theoral compositions wherein the weight ratio of tetrapotassiumpyrophosphate to tetrasodium pyrophosphate is from about 4.3:2.7 toabout 6:1 is especially preferred.

In order to optimize the anticalculus effectiveness of the oralcomposition, inhibitors against enzymatic hydrolysis of thepolyphosphate are desirably present. Such agents are an amount of afluoride ion source sufficient to supply 25 ppm. to 5,000 ppm. offluoride ions, and 0% to 3% of a synthetic anionic polymericpolycarboxylate having a molecular weight of about 1,000 to about1,000,000, preferably about 30,000 to about 500,000.

The sources of fluoride ions, or fluorine-providing component, as acidphosphatase and pyrophosphatase enzyme inhibitor component, are wellknown in the art as anti-caries agents. These compounds may be slightlysoluble in water or may be fully water-soluble. They are characterizedby their ability to release fluoride ions in water and by freedom fromundesired reaction with other compounds of the oral preparation. Amongthese materials are inorganic fluoride salts, such as soluble alkalimetal, alkaline earth metal salts, for example, sodium fluoride,potassium fluoride, ammonium fluoride, calcium fluoride, a copperfluoride such as cuprous fluoride, zinc fluoride, barium fluoride,sodium flourosilicate, ammonium florosilicate, sodium fluorozirconate,sodium monofluorophosphate, aluminum mono- and di-fluorophosphate, andfluorinated sodium calcium pyrophosphate. Alkali metal and tinfluorides, such as sodium and stannous fluorides, sodiummonofluorophosphate (MFP) and mixtures thereof, are preferred.

The amount of fluorine-providing compound is dependent to some extentupon the type of compound, its solubility, and the type or oralpreparation, but it must be a non-toxic amount, generally about 0.005 toabout 3.0% in the preparation. In a dentifrice preparation, e.g. dentalgel, toothpaste (including cream), toothpowder, or dental tablet, anamount of such compound which releases up to about 5,000 ppm of F ion byweight of the preparation is considered satisfactory. Any suitableminimum amount of such compound may be used, but it is preferable toemploy sufficient compound to release about 300 to 2,000 ppm, morepreferable about 800 to about 1,500 ppm of fluoride ion.

Typically, in the cases of alkali metal fluorides, this component ispresent in an amount up to about 2% by weight, based on the weight ofthe preparation, and preferably in the range of about 0.05% to 1%. Inthe case of sodium monofluorophosphate, the compound may be present inan amount of about 0.1-3%, more typically about 0.76%.

In dentifrice preparations such as lozenges and chewing gum, thefluorine-providing compound is typically present in an amount sufficientto release up to about 500 ppm, preferably about 25 to 300 ppm by weightof fluoride ion. Generally about 0.005 to about 1.0 wt. % of suchcompound is present.

The synthetic anionic polymeric polycarboxylate is an inhibitor ofalkaline phosphatase enzyme. Synthetic anionic polymericpolycarboxylates and their complexes with various cationic germicides,zinc and magnesium have been previously disclosed as anticalculus agentsper se in, for example U.S. Pat. No. 3,429,963 to Shedlovsky; U.S. Pat.No. 4,152,420 to Gaffar; U.S. Pat. No. 3,956,480 to Dichter et al; U.S.Pat. No. 4,138,477 to Gaffar; and U.S. Pat. No. 4,183,914 to Gaffar etal. However, only in aforementioned U.S. Pat. No. 4,627,977 to Gaffar etal is there disclosed use of such polycarboxylates for inhibitingsalivary hydrolysis of pyrophosphate anticalculus agents, in combinationwith a compound providing a source of fluoride ion. It is to beunderstood that the synthetic anionic polymeric polycarboxylates sodisclosed in these several patents are operative in the compositions andmethods of this invention and such disclosures are to that extentincorporated herein by reference thereto.

The synthetic anionic polymeric polycarboxylates optionally butpreferably employed herein are, as indicated above, well known, beingoften employed in the form of their free acids or preferably partiallyor more preferably fully neutralized water soluble alkali metal (e.g.potassium and preferably sodium) or ammonium salts. Preferred are 1:4 to4:1 copolymers of maleic anhydride or acid with another polymerizableethylenically unsaturated monomer, preferably methyl vinyl ether, havinga molecular weight (M.W.) of about 30,000 to about 1,000,000. Thesecopolymers are available for example as Gantrez AN 139 (M.W. 500,000),A.N. 119 (M.W. 250,000) and preferably S-97 Pharmaceutical Grade (M.W.70,000), of GAF Corporation. The term "synthetic" is intended to excludeknown thickening or gelling agents comprising carboxymethylcellulose andother derivatives of cellulose and natural gums.

Other operative polymeric polycarboxylates include those disclosed inU.S. Pat. No. 3,956,480 referred to above, such as the 1:1 copolymers ofmaleic anhydride with ethyl acrylate, hydroxyethyl methacrylate,N-vinyl-2-pyrollidone, or ethylene, the latter being available forexample as Monsanto EMA No. 1103, M.W. 10,000 and EMA Grade 61, and 1:1copolymers of acrylic acid with methyl or hydroxyethyl methacrylate,methyl or ethyl acrylate, isobutyl vinyl ether or N-vinyl-2-pyrrolidone.

Additional operative polymeric polycarboxylates disclosed in abovereferred to U.S. Pat. No. 4,138,477 and 4,183,914, include copolymers ofmaleic anhydride with styrene, isobutylene or ethyl vinyl ether,polyacrylic, polyitaconic and polymaleic acids, and sulfoacrylicoligomers of M.W. as low as 1,000, available as Uniroyal ND-2.

Suitable generally are polymerized olefinically or ethylenicallyunsaturated carboxylic acids containing an activated carbon-to-carbonolefinic double bond and at least one carboxyl group, that is, an acidcontaining an olefinic double bond which readily functions inpolymerization because of its presence in the monomer molecule either inthe alpha-beta position with respect to a carboxyl group or as part of aterminal methylene grouping. Illustrative of such acids are acrylic,methacrylic, ethacrylic, alpha-chloroacrylic, crotonic, beta-acryloxypropionic, sorbic, alpha-chlorsorbic, cinnamic, beta-styrylacrylic,muconic, itaconic, citraconic, mesaconic, glutaconic, aconitic,alpha-phenylacrylic, 2-benzyl acrylic, 2-cyclohexylacrylic, angelic,umbellic, fumaric, maleic acids and anhydrides. Other different olefinicmonomers copolymerizable with such carboxylic monomers includevinylacetate, vinyl chloride, dimethyl maleate and the like. Copolymerscontain sufficient carboxylic salt groups for water-solubility.

Also useful herein are so-called carboxyvinyl polymers disclosed astoothpaste components in U.S. Pat. No. 3,980,767 to Chown et al; U.S.Pat. No. 3,935,306 to Roberts et al; U.S. Pat. No. 3,919,409 to Perla etal; U.S. Pat. No. 3,911,904 to Harrison, and U.S. Pat. No. 3,711,604 toColodney et al. They are commercially available for example under thetrademarks Carbopol 934, 940 and 941 of B. F. Goodrich, these productsconsisting essentially of a colloidally water-soluble polymer ofpolyacrylic acid crosslinked with from about 0.75% to about 2.0% ofpolyallyl sucrose or polyallyl pentaerythritol as cross linking agent.

The synthetic anionic polymeric polycarboxylate component is mainly ahydrocarbon with optional halogen and O-containing substituents andlinkages as present in for example ester, ether and OH groups, and whenpresent is generally employed in the instant compositions in approximateweight amounts of 0.05 to 3%, preferably 0.05 to 2%, more preferably 0.1to 2%. Amounts in the upper portions of these ranges are typicallyemployed in dentifrice compositions typically containing a dentalabrasive and used in conjunction with brushing of the teeth, e.g. toothpastes (including creams), gels, powders and tablets. Amounts in excessof these ranges may be employed for thickening or gelling purposes.

As indicated above, these polymeric polycarboxylates have been found tobe effective inhibitors of alkaline phosphatase enzyme. Since thisenzyme has little activity (for hydrolyzing pyrophosphate) at about pH7.0 or below, the polymeric polycarboxylate component may, if desired,be omitted from oral preparations formulated to operate at such pH of7.0 or below. Such omission however could reduce the versatility andanticalculus effectiveness of the present oral compositions over thebroad pH range of about 4.5 to about 10.

In oral preparations such as mouthwashes, lozenges and chewing gum, thefluorine-providing compound may be typically present in an amountsufficient to release up to about 500 ppm, preferably about 25 to about300 ppm by weight of fluoride ion. Generally about 0.005 to about 1.0wt. % of such compound is present.

In certain highly preferred forms of the invention the oral compositionmay be substantially liquid in character, such as a mouthwash or rinse.In such a preparation the vehicle is typically a water-alcohol mixturedesirably including a humectant as described below. Generally, theweight ratio of water to alcohol is in the range of from about 1:1 toabout 20:1, preferably about 3:1 to 10:1 and more preferably about 4:1to about 6:1. The total amount of water-alcohol mixture in this type ofpreparation is typically in the range of from about 70 to about 99.9% byweight of the preparation. The alcohol is typically ethanol orisopropanol. Ethanol is preferred.

The pH of such liquid and other preparations of the invention isgenerally in the range of from about 4.5 to about 9 and typically fromabout 5.5 to 8. The pH is preferably in the range of from about 6 toabout 8.0. It is noteworthy that the compositions of the invention maybe applied orally at a pH below 5 without substantially decalcifying orotherwise damaging dental enamel. The pH can be controlled with acid(e.g. citric acid or benzoic acid) or base (e.g. sodium hydroxide) orbuffered (as with sodium citrate, benzoate, carbonate, or bicarbonate,disodium hydrogen phosphate, sodium dihydrogen phosphate, etc.).

In certain other desirable forms of this invention, the oral compositionmay be substantially solid or pasty in character, such as toothpowder, adental tablet or a dentifrice, that is a toothpaste (dental cream) orgel dentifrice. The vehicle of such solid or pasty oral preparationsgenerally contains dentally acceptable polishing material. Examples ofpolishing materials are water-insoluble sodium metaphosphate, potassiummetaphosphate, tricalcium phosphate, dihydrated calcium phosphate,anhydrous dicalcium phosphate, calcium pyrophosphate, magnesiumorthophosphate, trimagnesium phosphate, calcium carbonate, aluminumsilicate, zirconium silicate, silica, bentonite, and mixtures thereof.Other suitable polishing material include the particulate thermosettingresins described in U.S. Pat. No. 3,070,510 of Dec. 15, 1962 such asmelamine-, phenolic, and urea-formaldehydes, and cross-linkedpolyepoxides and polyesters. Preferred polishing materials includecrystalline silica having particle sizes of up to about 5 microns, amean particle size of up to about 1.1 microns, and a surface area of upto about 50,000 cm.² /gm., silica gel or colloidal silica, and complexamorphous alkali metal aluminosilicate.

When visually clear gels are employed, a polishing agent of colloidalsilica, such as those sold under the trademark SYLOID as Syloid 72 andSyloid 74 or under the trademark SANTOCEL as Santocel 100 alkali metalalumino-silicate complexes are particularly useful, since they haverefractive indices close to the refractive indices of gellingagent-liquid (including water and/or humectant) systems commonly used indentifices.

Many of the so-called "water-insoluble" polishing materials are anionicin character and also include small amounts of soluble material. Thus,insoluble sodium metaphosphate may be formed in any suitable manner asillustrated by Thorpe's Dictionary of Applied Chemistry, Volume 9, 4thEdition, pp. 510-511. The forms of insoluble sodium metaphosphate knownas Madrell's salt and Kurrol's salt are further examples of suitablematerials. These metaphosphate salts exhibit only a minute solubility inwater, and therefore are commonly referred to as insolublemetaphosphates (IMP). There is present therein a minor amount of solublephosphate material as impurities, usually a few percent such as up to 4%by weight. The amount of soluble phosphate material, which is believedto include a soluble sodium trimetaphosphate in the case of insolublemetaphosphate, may be reduced or eliminated by washing with water ifdesired. The insoluble alkali metal metaphosphate is typically employedin powder form of a particle size such that no more than 1% of thematerial is larger than 37 microns.

The polishing material is generally present in the solid or pastycompositions in weight concentrations of about 10% to about 99%.Preferably, it is present in amounts ranging from about 10% to about75%. in toothpaste, and from about 70% to about 99% in toothpowder.

In a toothpaste, the liquid vehicle may comprise water and humectanttypically in an amount ranging from about 10% to about 80% by weight ofthe preparation. Glycerine, propylene glycol, sorbitol, polypropyleneglycol and/or polyethylene glycol (e.g. 400-600) exemplify suitablehumectants/carriers. Also advantageous are liquid mixtures of water,glycerine and sorbitol. In clear gels where the refractive index is animportant consideration, about 3-30 wt. % of water, 0 to about 70 wt. %of glycerine and about 20-80 wt. % of sorbitol are preferably employed.

Toothpastes, creams and gels typically contain a natural or syntheticthickener or gelling agent in proportions of about 0.1 to about 10,preferably about 0.5 to about 5 wt. %. A suitable thickener is synthetichectorite, a synthetic colloidal magnesium alkali metal silicate complexclay avaiable for example as Laponite (e.g. CP, SP 2002, D) marketed byLaporte Industries Limited. Laponite D analysis shows, approximately byweight, 58.00% SiO₂, 25.40% MgO, 3.05% Na₂ O, 0.98% Li₂ O, and somewater and trace metals. Its true specific gravity is 2.53 and it has anapparent bulk density (g./ml. at 8% moisture) of 1.0.

Other suitable thickeners include Irish moss, gum tragacanth, starch,polyvinylpyrrolidone, hydroxyethypropylcellulose, hydroxybutyl methylcellulose, hydroxypropyl methyl cellulose, hydroxyethyl cellulose (e.g.available as Natrosol), sodium carboxymethyl cellulose, and colloidalsilica such as finely ground Syloid (e.g. 244).

It will be understood that, as is conventional, the oral preparationsare to be sold or otherwise distributed in suitable labelled packages.Thus a jar of mouthrinse will have a label describing it, in substance,as a mouthrinse or mouthwash and having directions for its use; and atoothpaste, cream or gel will usually be in a collapsible tube,typically aluminum, lined lead or plastic, or other squeeze, pump orpressurized dispenser for metering out the contents, having a labeldescribing it, in substance, as a toothpaste, gel or dental cream.

Organic surface-active agents are used in the compositions of thepresent invention to achieve increased prophylactic action, assist inachieving thorough and complete dispersion of the anticalculus agentthroughout the oral cavity, and render the instant compositions morecosmetically acceptable. The organic surface-active material ispreferably anionic, nonionic or ampholytic in nature, and it ispreferred to employ as the surface-active agent a detersive materialwhich imparts to the composition detersive and foaming properties.Suitable examples of anionic surfactants are water-soluble salts ofhigher fatty acid monoglyceride monosulfates, such as the sodium salt ofthe monosulfated monoglyceride of hydrogenated coconut oil fatty acids,higher alkyl sulfates such as sodium lauryl sulfate, alkyl arylsulfonates such as sodium dodecyl benzene sulfonate, higher alkylsulfoacetates, higher fatty acid esters of 1,2-dihydroxy propanesulfonate, and the substantially saturated higher aliphatic acyl amidesof lower aliphatic amino carboxylic acid compounds, such as those having12 to 16 carbons in the fatty acid, alkyl or acyl radicals, and thelike. Examples of the last mentioned amides are N-lauroyl sarcosine, andthe sodium, potassium, and ethanolamine salts of N-lauroyl, N-myristoyl,or N-palmitoyl sarcosine which should be substantially free from soap orsimilar higher fatty acid material. The use of these sarcosinatecompounds in the oral compositions of the present invention isparticularly advantageous since these materials exhibit a prolonged andmarked effect in the inhibition of acid formation in the oral cavity dueto carbohydrate breakdown in addition to exerting some reduction in thesolubility of tooth enamel in acid solutions. Examples of water-solublenonionic surfactants are condensation products of ethylene oxide withvarious reactive hydrogen-containing compounds reactive therewith havinglong hydrophobic chains (e.g. aliphatic chains of about 12 to 20 carbonatoms), which condensation products ("ethoxamers") contain hydrophilicpolyoxyethylene moieties, such as condensation products of poly(ethyleneoxide) with fatty acids, fatty alcohols, fatty amides, polyhydricalcohols (e.g. sobitan monosterate) and polypropyleneoxide (e.g.Pluronic materials).

Various other materials may be incorporated in the oral preparations ofthis invention such as whitening agents, preservatives, silicones,chlorophyll compounds and/or ammoniated material such as urea,diammonium phosphate, and mixutes thereof. These adjuvants, wherepresent, are incorporated in the preparations in amounts which do notsubstantially adversely affect the properties and characteristicsdesired. Significant amounts of zinc, magnesium and other metal saltsand materials, generally soluble, which would complex with activecomponents of the instant invention are to be avoided.

Any suitable flavoring or sweetening material may also be employed.Examples of suitable flavoring constituents are flavoring oils, e.g. oilof spearmint, pepperment, wintergreen, sassafras, clove, sage,eucalyptus, marjoram, cinnamon, lemon, and orange, and methylsalicylate. Suitable sweetening agents include sucrose, lactose,maltose, sorbitol, xylitol, sodium cyclamate, perillartine, AMP(aspartyl phenyl alanine, methyl ester), saccharine and the like.Suitably, flavor and sweetening agents may together comprise from about0.1% to 5% more of the preparation.

In the preferred practice of this invention an oral compositionaccording to this invention such as a mouthwash or dentifrice containingthe composition of the present invention is preferably applied regularlyto dental enamel, such as every day or every second or third day orpreferably from 1 to 3 times daily, at a pH of about 4.5 to about 9,generally about 5.5 to about 8, preferably about 6 to 8, for at least 2weeks up to 8 weeks or more up to lifetime.

The compositions of this invention can be incorporated in lozenges, orin chewing gum or other products, e.g. by stirring into a warm gum baseor coating the outer surface of a gum base, illustrative of which may bementioned jelutone, rubber latex, vinylite resins, etc., desirably withconventional plasticizers or softeners, sugar or other sweeteners orcarbohydrates such as glucose, sorbitol and the like.

The following examples are further illustrative of the nature of thepresent invention, but it is understood that the invention is notlimited thereto. All amounts and proportions referred to herein and inthe appended claims are by weight.

EXAMPLE 1

Slurries and solutions described below are prepared to determineeffectiveness in terms of minimum inhibitory concentration (MIC) ofvarious antibacterial agents against a variety of oral bacterialorganisms implicated in formation of plaque and leading to gingivitis ondental surfaces. Soft plaque contains about 1.7×10¹¹ organism/gm. (netweight). The antibacterial agents are admixed with anionic materials,particularly anionic surface active agent often commonly employed inoral compositions and polyphosphate anticalculus agent.

Minimum inhibitory concentration (MIC) of antibacterial agent is used toevaluate the efficacy of the agent in vitro. MIC is defined as theminimum concentration in micrograms/ml of antibacterial agent at whichthe growth of bacteria is completely inhibited by the agent. The smallerthe MIC value the greater is the efficacy of the antibacterial agent toinhibit the growth of the bacteria. The in vitro MIC data is related tothe efficacy of the dentifrice in vivo since retention and release ofantibacterial agent into the oral cavity after toothbrushing is in therange of mcg/ml.

In the Tables, following disclosure and following Examples, the agentTriclosan, 2,4,4'-trichloro-2'-hydroxydiphenyl ether is indicated as"TCHE"; the quaternary ammonium antibacterial agents benzethoniumchloride is indicated as "BTC"; The biguanide chlorhexidine digluconateis indicated as "CH", sodium lauryl sulfate is indicated as "SLS"; thecopolymer of maleic anhydride and methyl vinyl ether available from GAFcorporation as "Gantrez S-97" is identified as "Gantrez"; tetrasodiumpyrophosphate is identified as "pyrophosphate"; and sodium fluoride isidentified as "NaF".

                                      TABLE 1                                     __________________________________________________________________________                Minimum Inhibition Concentration                                              (MIC)                                                                         in mcg/ml                                                                                 Actinobacillus                                        Test        Bacteriodes                                                                         Bacteriodes                                                                         actinomyce-                                                                          Streptococcus                                  Solution    gingivalis                                                                          intermedius                                                                         temcomitans                                                                          mutans                                         __________________________________________________________________________      0.5% TCHE and                                                                           2.5   2.5   5.0    25.0                                             1% SLS in                                                                     water                                                                         0.5% TCHE,                                                                              2.5   2.5   5.0    25.0                                             1% SLS,                                                                       1% Gantrez,                                                                   2% Pyrophosphate                                                              and 0.2% NaF in                                                               water                                                                         1% SLS in NE    NE    NE     NE                                               water                                                                         1% SLS,   NE    NE    NE     NE                                               1% Gantrez and                                                                2% Pyrophosphate                                                              in water                                                                    __________________________________________________________________________     note:                                                                         NE = not effective                                                       

The results indicate that TCHE in the presence of anionic surfactantinhibited four dental plaque organisms, Bacteriodes gingivalis,Bacteroides intermedius, Actinobacillus actinomycetemcomitans and Strep.mutans at 2.5 mcg/ml and 2.5 mcg/ml, 5.0 mcg/ml and 25.0 mcg/mlrespectively(1). Similar antibacterial effect is seen in the presence ofGantrez/pyrophosphate/fluoride(2). SLS per se and a combination ofSLS/Gantrez/pyrophosphate/fluoride was ineffective(3 and 4).

It is noteworthy that in human clinical tests with cationicantibacterial agents, 0.075% BTC dissolved in water is effective inreducing plaque formation while 0.075% BTC and 1% pyrosphosphatedissolved in water is not. Similarly, 0.1% CH dissolved in water iseffective in reducing plaque formation while 0.1% CH and 1% sodiumN-lauroyl sarcosinate dissolved in water is not.

EXAMPLE 2

The adsorption to and release from tooth minerals forantiplaque/antitartar efficacy of agents is assessed by adsorption ofantibacterial agent to saliva coated tooth mineral hydroxyapatite in thepresence and the absence of pyrophosphate (soluble tetrasodiumpyrophosphate)/Gantrez/NaF.

200 mg. of hydroxyapatite (HA) is treated with human saliva for 2 hours.The excess saliva is washed off with a buffer and saliva coated HA isused for adsorption studies. Various concentrations of TCHE in SLS or inSLS/pyrophosphate/Gantrez/NaF are mixed with the coated HA and incubatedat 37° for 3 hours under continuous agitation. At the end of incubationperiod, the mixtures are centrifuged, HA separated and the amounts ofTCHE adsorbed determined by estimating TCHE in the supernatant at 283 nMin a Gilford spectrophotometer. The amounts adsorbed are calculated bythe difference between the amount added and the amount left in thesupernatant after the incubation with coated HA. The table belowsummarizes the data.

                  TABLE 2                                                         ______________________________________                                                          % of TCHE                                                   Components and Concentrations                                                                   Adsorbed to Coated HA                                       ______________________________________                                        0.005% TCHE in 1% SLS                                                                           80%                                                         0.01% TCHE in 1% SLS                                                                            85%                                                         0.015% TCHE in 1% SLS                                                                           85%                                                         0.02% TCHE in 1% SLS                                                                            88%                                                         0.005% TCHE in 1% SLS; 0.5%                                                                     80%                                                         Gantrez; 2% pyrophosphate/                                                    0.24% NaF                                                                     0.01% TCHE in 1% SLS; 0.5%                                                                      85%                                                         Gantrez; 2% pyrophosphate/                                                    0.24% NaF                                                                     0.015% TCHE in 1% SLS; 0.5%                                                                     86%                                                         Gantrez; 2% pyrophosphate/                                                    0.24% NaF                                                                     0.02% TCHE in 1% SLS; 0.5%                                                                      87%                                                         Gantrez; 2% pyrophosphate/                                                    0.24% NaF                                                                     ______________________________________                                    

The data indicates that the addition of pyrophosphate/Gantrez/NaF doesnot impair adsorption of TCHE to saliva coated tooth minerals.

EXAMPLE 3

    ______________________________________                                        Dentifrice  A          B          C                                           Compositions                                                                              Parts      Parts      Parts                                       ______________________________________                                        Glycerine   15.00      10.20      15.00                                       Polyethylene                                                                              5.00       3.00       5.00                                        Glycol 600                                                                    Iota Carrageenan                                                                          0.60       --         0.60                                        Sodium      --         1.00       --                                          Carboxymethyl                                                                 Cellulose                                                                     Sodium Saccharin                                                                          0.40       --         0.40                                        Sodium Cyclamate                                                                          --         3.00       --                                          Sodium Fluoride                                                                           0.243      0.243      0.243                                       Deionized water                                                                           15.08      29.907     23.657                                      Deionized water                                                                           15.08      29.907     23.657                                      Titanium Dioxide                                                                          --         --         0.50                                        Sodium Benzoate                                                                           --         0.50       --                                          FD & C Blue No. 1                                                                         0.400      --         --                                          (1% Solution)                                                                 Sorbitol (70%)                                                                            19.807     22.50      22.50                                       Gantrez S-97                                                                              8.330(*)   1.00(**)   1.00(**)                                    Tetrasodium 1.50       1.50       1.50                                        Pyrophosphate                                                                 Tetrapotassium                                                                            4.50       4.50       4.50                                        Pyrophosphate                                                                 Precipitated                                                                              16.00      19.50      --                                          Amorph.                                                                       Hydrated Silica                                                               Precipitated Amorp.                                                                       --         --         16.00                                       Silica containing                                                             combined alumina                                                              Silica Thickener                                                                          7.00       --         5.50                                        Flavor      1.10       0.95       1.10                                        Sodium Lauryl                                                                             1.20       1.20       1.20                                        Sulfate                                                                       TCHE        0.50       0.50       0.50                                        ______________________________________                                         *liquid (13% aqueous)                                                         **powder                                                                 

EXAMPLE 4

The dentifrice described in Example 3A is compared with the samecomposition except without any TCHE and with added 0.50 parts of water.Aqueous extracts of each dentifrice are prepared as follows: 50 ml ofdistilled water is added to 1.0 gm of each dentifrice, mixed well for acouple of hours with stirring bar and centrifuged, after which thesupernatant is collected as aqueous extract. Antibacterial activity ofthe dentifrice extracts are evaluated on Bacteriodes gingivalis. Resultsare summarized below.

                  TABLE 3                                                         ______________________________________                                                              Inhibition of                                                                 Growth of                                                                     Bacteriodes Gingivalis                                  Treatment             %                                                       ______________________________________                                        Extract from dentifrice containing                                                                  100.0                                                   TCHE (1:500)                                                                  Extract from dentifrice without                                                                     0.0                                                     TCHE (1:500)                                                                  TCHE (5.0 mcg/ml) by itself                                                                         100.0                                                   ______________________________________                                    

These results indicate that TCHE antibacterial antiplaque agent iscompatible in a dentifrice composition containing anionic surfactantplus pyrophosphate anticalculus ingredients with enzyme inhibitorsGantrez and NaF. Similar comparable effects prevail when each of hexylresorcinol and 2,2'-methylene bis(4-chloro-6-bromophenol) replace TCHE.

EXAMPLE 5

    ______________________________________                                        Mouthrinse                  Parts                                             ______________________________________                                        Tetrasodium Pyrophosphate        2.00                                         Gantrez S-97                     0.25                                         Glycerine                        10.00                                        Sodium Fluoride                  0.05                                         Pluronic F108                    2.00                                         (Polyoxyethylene/Polyoxypropylene                                             Block Copolymer)                                                              TCHE                             0.10                                         Flavor                           0.40                                         Water                  Q. S. to 100.00                                        ______________________________________                                    

EXAMPLE 6

    ______________________________________                                        Lozenge                                                                       ______________________________________                                        75-80% Sugar                                                                  1-20% Corn Syrup                                                              0.1-1.0 Flavor                                                                2% Tetrasodium Pyrophosphate                                                  0.25% Gantrez S-97                                                            0.01 to 0.05% NaF                                                             0.01 to 0.1% TCHE                                                             1 to 5% Magnesium Stearate Lubricant                                          0.01 to 0.2% Water                                                            ______________________________________                                    

EXAMPLE 7

    ______________________________________                                        Chewing Gum              Parts                                                ______________________________________                                        Gum base                      25.00                                           Sorbitol (70%)                17.00                                           TCHE                          0.10 to 0.50                                    Tetrasodium Pyrophosophate    2.00                                            Gantrez S.97                  0.25                                            NaF                           0.05                                            Glycerine                     0.50                                            Crystalline Sorbitol          53.00                                           Flavor and Water    Q. S. to 100.00                                           ______________________________________                                    

This invention has been described with respect to certain preferredembodiments and it will be understood that modifications and variationsthereof obvious to those skilled in the art are to be included withinthe purview of this application and the scope of the appended claims.

We claim:
 1. An oral composition comprising, in an orally acceptablevehicle, an effective anticalculus amount of at least one water solublelinear molecularly dehydrated polyphosphate salt as essentialanticalculus agent, an effective antiplaque amount of a substantiallywater insoluble noncationic antibacterial compound as essentialantiplaque agent, and:A. an amount of a fluoride ion-providing sourcesufficient to supply about 25 ppm. to about 2,000 ppm. of fluoride ions;or B. about 0.05% to about 3% of a water soluble synthetic anionicpolymeric polycarboxylate; or C. mixtures of A and B.
 2. An oralcomposition according to claim 1 containing A wherein said fluorideion-providing source comprises sodium fluoride, sodiummonofluorophosphate, or a mixture thereof.
 3. An oral compositionaccording to claim 1 containing B or C wherein said fluorideion-providing source comprises sodium fluoride, sodiummonofluorophosphate or a mixture thereof and said polycarboxylatecomprises a salt of a copolymer of maleic acid or anhydride withmethylvinylether.
 4. An oral composition according to claim 3 whereinsaid antibacterial compound comprises a halogenated diphenyl ether. 5.An oral composition according to claim 4 wherein said antibacterialcompound comprises Triclosan.
 6. An oral composition according to anyone of claims 1 to 5 in the form of a toothpaste, cream or gelcontaining a dentally acceptable polishing agent.
 7. An oral compositionaccording to any one of claims 1 to 5 in the form of a mouthwashcontaining a water/humectant vehicle.
 8. An oral composition comprising,in an orally acceptable vehicle, a dentally acceptable silica polishingagent, an effective anticalculus amount of at least one water solublelinear molecularly dehydrated polyphosphate salt as essentialanticalculus agent, an effective antiplaque amount of a substantiallywater insoluble noncationic antibacterial compound as essentialantiplaque agent, and:A. an amount of a fluoride ion-providing sourcesufficient to supply about 25 ppm. to about 2,000 ppm. of fluoride ions;or B. about 0.05% to about 3% of a water soluble synthetic anionicpolymeric polycarboxylate; or C. mixtures of A and B.
 9. A method ofinhibiting dental plaque and calculus comprising applying to teethplaque and calculus inhibiting amounts of an oral composition as definedin any one of claims 1 to 5 and 8.